The aim of this study was to evaluate the therapeutic effects of vitamin K2 (VK2) on castration-resistant prostate cancer (CRPC) and its anti-cancer mechanisms in a pre-clinical study using a VCaP cell line (ATCC ® CRL-2876™) which was established from a vertebral bone metastasis from a patient with hormone refractory prostate cancer. Our data showed that VK2 significantly inhibited CRPC VCaP cell proliferation in a dosedependent manner at 48 h treatment in vitro. In addition, VK2 reduced the migration potential of VCaP cells and inhibited anchorage-independent growth of these cells...

Therapeutic agents are urgently needed for treating metastatic castration-refractory prostate cancer (mCRPC) that is unresponsive to androgen deprivation and chemotherapy. Our screening assays demonstrated that chemotherapy-resistant prostate cancer (PCa) cells are more sensitive to HDAC inhibitors than paired sensitive PCa cells, as demonstrated by cell proliferation and apoptosis in vitro and in vivo. Kinetic study revealed that TSA-induced apoptosis was significantly dependent on enhanced transcription and protein synthesis in an early stage, which subsequently caused ER stress and apoptosis...

Rationale: Docetaxel-mediated chemotherapy is the first-line standard approach and has been determined to show a survival advantage for metastatic castration-resistant prostate cancer (mCRPC) patients. However, a substantial proportion of patients eventually becomes refractory due to drug resistance. The detailed mechanisms remain unclear. We have previously reported that Prostate Leucine Zipper (PrLZ), a specific oncogene of prostate cancer (PCa), promotes PCa cell growth at the castration-resistant stage, thus suggesting a vital role of PrLZ in the progression of CRPC...

Docetaxel is the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients ultimately become refractory due to the development of docetaxel resistance. The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC...

INTRODUCTION: This multicenter phase 2 study assessed the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: We enrolled 77 patients who had received no prior chemotherapy for CRPC between 1998 and 2000; a total of 74 subjects were eligible for the study. Each 8-week cycle included paclitaxel 90 mg/m2 provided intravenously weekly for 6 weeks, followed by 2 weeks off therapy and oral estramustine 280 mg twice daily for 3 days beginning 24 hours before the first dose of paclitaxel...

Activation of the NFκB pathway is often associated with advanced cancer and has thus been regarded as a rational therapeutic target. Wedelia chinensis is rich in luteolin, apigenin, and wedelolactone that act synergistically to suppress androgen receptor activity in prostate cancer. Interestingly, our evaluation of a standardized Wedelia chinensis herbal extract (WCE) concluded its efficacy on hormone-refractory prostate cancer through systemic mechanisms. Oral administration of WCE significantly attenuated tumor growth and metastasis in orthotopic PC-3 and DU145 xenografts...

The actual strategy to improve current therapies in advanced prostate cancer involves targeting genes activated by androgen withdrawal, either to delay or prevent the emergence of the castration-refractory phenotype. However, these genes are often implicated in several physiological processes, and long-term inhibition of survival proteins might be accompanied with cytotoxic effects. To avoid this problem, an alternative therapeutic strategy relies on the identification and use of compounds that disrupt specific protein-protein interactions involved in androgen withdrawal...

BACKGROUND: The androgen receptor (AR) is the classical target for prostate cancer prevention and treatment, but more recently estrogens and their receptors have also been implicated in prostate cancer development and tumor progression. METHODS: Recent experimental and clinical data were reviewed to elucidate pathogenetic mechanisms how estrogens and their receptors may affect prostate carcinogenesis and tumor progression. RESULTS: The estrogen receptor beta (ERβ) is the most prevalent ER in the human prostate, while the estrogen receptor alpha (ERα) is restricted to basal cells of the prostatic epithelium and stromal cells...

AIMS: Ferroportin (FPN) is an iron exporter that plays an important role in cellular and systemic iron metabolism. Our previous work has demonstrated that FPN is decreased in prostate tumors. We sought to identify molecular pathways regulated by FPN in prostate cancer (PC) cells. RESULTS: We show that overexpression of FPN induces profound effects in cells representative of multiple histological subtypes of PC by activating different but converging pathways. Induction of FPN induces autophagy and activates the transcription factors p53 and KLF6 and their common downstream target, p21...

Since November 2013, the alpha emitter radium-223 dichloride (Alpharadin/Xofigo®) has been approved for the treatment of men with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. In the ASYMPCA clinical trial, radium-223 was shown to improve overall survival and to reduce the time to the first symptomatic skeletal event. The use of radium-223 was associated with a reduction of pain and an improvement of health-related quality of life compared to the placebo arm...

Docetaxel-based chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (CRPC). However, a number of patients with metastatic CRPC are refractory to docetaxel or develop docetaxel resistance. The underlying molecular mechanisms of docetaxel resistance remain unclear, which is a significant burden to the management of metastatic prostate cancer. In the present study, the differential gene expression between docetaxel-sensitive (PC3) and docetaxel-resistant (PC3DR2) prostate cancer cells was identified using DNA microarrays, western blot analysis and reverse transcription-quantitative polymerase chain reaction...

INTRODUCTION: Since just after the year 2000 in Quebec, the management of metastatic castration-resistant prostate cancer (mcrpc) has evolved considerably, with the inclusion of docetaxel-based chemotherapy, bone-targeted therapies (zoledronic acid and denosumab), and more recently, abiraterone, enzalutamide, and cabazitaxel for docetaxel-refractory patients. In the present study, we aimed to analyze contemporary mcrpc management patterns and therapy utilization trends in Quebec. METHODS: The study cohort consisted of patients dying of prostate cancer (pca) between January 2001 and December 2013, selected from Quebec public health care insurance databases...

Theranostics, a modern approach combining therapeutics and diagnostics, is among the most promising concepts in nuclear medicine for optimizing and individualizing treatments for many cancer entities. Theranostics has been used in clinical routines in nuclear medicine for more than 60 y-as (131)I for diagnostic and therapeutic purposes in thyroid diseases. In this minireview, we provide a survey of the use of 2 different radioiodine isotopes for targeting the sodium-iodine symporter in thyroid cancer and nonthyroidal neoplasms as well as a brief summary of theranostics for neuroendocrine neoplasms and metastatic castration-refractory prostate cancer...

Cabazitaxel is an effective chemotherapeutic agent used in the treatment of metastatic castration-resistant prostate cancer (mCRPC) refractory to docetaxel. With the advent of new antiandrogen therapies, immune-based treatments, and radioactive-targeted therapy, there are now multiple effective and approved agents for this disease state. The optimal sequencing of these agents is unclear as there are no large-scale head-to-head comparisons. Clinicians must familiarize themselves with the most recent studies as well as drug toxicities to determine the best treatment option for their patients...

The androgen receptor (AR) plays important roles in prostate cancer development and prostate tumor growth. After binding to androgens, AR functions as a nuclear receptor and translocates to the nucleus to bind to specific AR-binding sites (ARBSs). AR regulates epigenetic factor recruitments to activate its downstream signaling. Although androgen deprivation therapy (ADT) is initially useful for prostate cancer patients, most patients eventually show resistance with hormone-refractory prostate cancers (HRPCs) or castration-resistant prostate cancers (CRPCs)...

BACKGROUND: Prostate cancer (PC) is the most common cancer in Western countries. More than one third of PC patients develop metastatic disease, and the 5-year expected survival in distant disease is about 35%. During the last few years, new treatments have been launched for metastatic castrate-resistant prostate cancer (mCRPC). OBJECTIVES: We aimed to review the current literature on health economic analysis on the treatment of metastatic prostate cancer (mPC), compare the studies, summarize the findings and make the results available to administrators and decision makers...

Androgen receptor (AR) signaling reprograms cellular metabolism to support prostate cancer (PCa) growth and survival. Another key regulator of cellular metabolism is mTOR, a kinase found in diverse protein complexes and cellular localizations, including the nucleus. However, whether nuclear mTOR plays a role in PCa progression and participates in direct transcriptional cross-talk with the AR is unknown. Here, via the intersection of gene expression, genomic, and metabolic studies, we reveal the existence of a nuclear mTOR-AR transcriptional axis integral to the metabolic rewiring of PCa cells...